Relative profiling of L-tryptophan derivatives from selected edible mushrooms as psychoactive nutraceuticals to inhibit P-glycoprotein: a paradigm to contest blood-brain barrier

Depression is a mental illness and is considered to be a global threat. It is designated as burden of disease. There is therefore an intense need to improve the therapeutic response of antidepressants. India beholds a wide fraction (Agaricus bisporus and Pleurotus ostreatus ) as a vital source of non-hallucinogenic indole compounds. The amino acids L-tryptophan and 5-hydroxytryptophan (5-HTP) are precursors of serotonin. 5-HTP is a potential antidepressant that can cross the blood-brain barrier (BBB) at a high rate and is converted into serotonin more efficiently. Drug delivery across this blockade remains a challenge due to the stimulation of efflux pump receptors called permeability glycoprotein (P-gp). This work reports a comparative phytochemical assay and profiling of non-hallucinogenic tryptophan metabolites using HPLC from two organic extracts of edible mushrooms. The efficacy of the eluted compounds was authenticated as P-gp inhibitors with in vitro and in silico studies. The following four derivatives were obtained from the methanol and ethanol extracts of the mushrooms: 5-hydroxy-L-tryptophan (5HTR), 5-hydroxy tryptamine (5-HT), L-tryptophan (L-Trp), and tryptamine (TA). In vitro and molecular docking studies targeting P-gp (minimum energy: -64.38 and -83.93 kcal/mol, respectively) substantiated the ability of mushroom-derived metabolites to facilitate drug delivery in the brain. This study verified that mushrooms containing non-hallucinogenic metabolites can act as psychoactive nutraceuticals that are significant for enhancing mental health. The high therapeutic efficacy, these mushrooms can serve as ideal neurological drug leads to fortify treatment for mental illness.